Liver histological reversibility of lamivudine in treatment-naïve children with chronic hepatitis B: a retrospective cohort study from a single center Shanghai China.

Background: Low viral load of hepatitis B virus (HBV) infection may also result in serious liver complications. Whether long-term suppression of HBV replication has beneficial effects on the reversibility of the liver histology associated with chronic hepatitis B (CHB) in children is unclear. This study assessed the histological response of lamivudine (LAM) in CHB children. Methods: Treatment-naïve CHB patients who 1≤ aged <18 years, indicating the immune-active phase, and receiving LAM were enrolled. Demographics, biochemical value, virology and histology, and safety were retrospectively analysed. Patients visit the hospital at baseline, every 12 weeks during treatment, and every 24 or 48 weeks after treatment withdrawal. Histological inflammatory improvement was defined as a ≥1-point decrease in the inflammatory score. Fibrosis regression was defined as a decrease of ≥1 point or no worsening of the fibrosis score. Results: Total 35 children enrolled, 13 of them were lost, and 22 patients remained in the study up to 10 years after treatment. Liver biopsy results both at baseline and before treatment withdrawal were available for 14 of the 22 patients. Of the 14 children, 78.6% were male and 78.6% were HBeAg-positive. At baseline, the mean age was 7.3±5.2 years. The serum HBV DNA level of 13 subjects was 7.3±1.3 log10 IU/m. and alanine aminotransferase (ALT) was 142±102 U/L. The mean inflammation score was 2.9±0.7. The mean fibrosis score was 3.7±0.8. The mean duration was 96.0±23.6 weeks (median 96 weeks). All patients (100%) had a normal ALT after a median 12-week treatment; after 24-week, HBV DNA were <1,000 IU/mL in 92.9%. At a median of 30-week, 100% of the HBeAg-positive patients showed HBeAg seroconversion; 7.1% exhibited HBsAg seroconversion after 24-week treatment. After a mean of 96-week, the 14 patients (100%) exhibited a mean 2.2-point inflammatory improvement from baseline (P<0.001), and 92.9% exhibited a mean 2.1-point fibrosis reduction (P<0.001). No virological breakthroughs or serious adverse events occurred. Conclusions: This study showed that 96-week mean duration of LAM may reverse advanced inflammation and fibrosis/cirrhosis in young CHB children.

The antioxidant effects of hedysarum polybotrys polysaccharide in extending lifespan and ameliorating aging-related diseases in Drosophila melanogaster.

Hedysarum polybotrys polysaccharide (HPS) is one of the main active ingredients of Hedysarum with many health-beneficial properties, including antioxidant property, immunomodulatory, anti-inflammatory, and anti-tumor. However, the effect of HPS on anti-aging is still unclear. This study was to explore the protective function of HPS on aging and age-related diseases using Drosophila melanogaster. The results demonstrated that HPS supplementation promoted hatchability and prolonged lifespan by enhancing the antioxidative capacity. Administraction of HPS ameliorated age-related symptoms such as imbalanced intestinal homeostasis, sleep disturbances, and beta-amyloid (Aß) induced Alzheimer's disease (AD) in flies, but did not modulate neurobehavioral deficits in the AD model of tauopathy and the Parkinson's disease (PD) model of Pink1 mutation. Overall, this study reveals that HPS has strong potential in the prevention of aging and age-related diseases, and provided a new candidate for the development of anti-aging drugs.

Exposure to cytarabine causes side effects on adult development and physiology and induces intestinal damage via apoptosis in Drosophila.

Cytarabine (Ara-C) is a widely used drug in acute myeloid leukemia (AML). However, it faces serious challenges in clinical application due to serious side effects such as gastrointestinal disorders and neurologic toxicities. Until now, the mechanism of Ara-C-induced damage is not clear. Here, we used Drosophila melanogaster (fruit fly) as the in vivo model to explore the side effects and mechanism of Ara-C. Our results showed that Ara-C supplementation delayed larval development, reduced lifespan, impaired locomotor capacity, and increased susceptibility to stress response in adult flies. In addition, Ara-C led to the intestinal morphological damage and ROS accumulation in the guts. Moreover, administration of Ara-C promoted gene expressions of Toll pathway, IMD pathway, and apoptotic pathway in the guts. These findings raise the prospects of using Drosophila as in vivo model to rapidly assess chemotherapy-mediated toxicity and efficiently screen the protective drugs.

Liver histology of treatment-naïve children with chronic hepatitis B virus infection in Shanghai China.

OBJECTIVES: Chronic hepatitis B (CHB) is associated with high morbidity and mortality. We aimed to investigate associations between hepatic histology and clinical characteristics in treatment-naïve children with CHB in Shanghai, China. METHODS: The liver biopsy specimens of 278 treatment-naïve children with CHB virus infection were scored for inflammation and fibrosis, and correlations with clinical and laboratory data were determined. RESULTS: CHB clinical, virologic, and pathologic features were studied in 278 treatment-naïve children (177 [63.7%] males) in Shanghai, China. Maternal sera were positive for hepatitis B surface antigen for 277 children. At biopsy, 87.4% of patients were hepatitis B e antigen-positive. The median age at biopsy was 5.1 years (interquartile range 2.8-8.4 years). Hepatitis B virus (HBV) deoxyribonucleic acid levels were generally high (mean 7.4 log10 IU/ml), as were levels of serum alanine aminotransferase (ALT, median 105 U/l). Using the Metavir histology activity index scoring system, no, mild, moderate, and severe inflammation were seen in 2.9%, 22.3%, 73.4%, and 1.4% of patients, respectively. No fibrosis, mild fibrosis, moderate fibrosis, and cirrhosis were seen in 11.5%, 32.7%, 47.5%, and 8.3% of patients, respectively. When the serum ALT level was ≤80 (two times the upper limit of normal) and >80 U/l, the inflammation score (P <0.0001) was significantly different, and the fibrosis score was also significantly different (P <0.0001). Inflammation and fibrosis were aggravated with increasing ALT levels. Fibrosis scores were significantly higher in children aged ≤3 than aged >3 years (P <0.0001). The rates of moderate fibrosis and cirrhosis were higher in children aged ≤3 years at biopsy. No correlations were found between histologic changes and sex, HBV genotype, or HBV deoxyribonucleic acid level. CONCLUSION: Substantial heterogeneity in inflammatory and fibrotic levels was observed in treatment-naïve children with CHB in Shanghai, China. Serum ALT levels >80 U/l may be a strong indicator of the degree of hepatic inflammation and fibrosis severity. Moderate fibrosis and cirrhosis can appear in children aged 3 years or younger.

Expression, Prognosis, and Immune Infiltrates Analyses of E2Fs in Human Brain and CNS Cancer.

OBJECTIVE: We investigated the expression patterns, potential functions, unique prognostic value, and potential therapeutic targets of E2Fs in brain and CNS cancer and tumor-infiltrating immune cell microenvironments. METHODS: We analyzed E2F mRNA expression levels in diverse cancer types via Oncomine and GEPIA databases, respectively. Moreover, we evaluated the prognostic values using GEPIA database and TCGAportal database and the correlation of E2F expression with immune infiltration and the correlation between immune cell infiltration and GBM and LGG prognosis via TIMER database. Then, cBioPortal, GeneMANIA, and DAVID databases were used for mutation analysis, PPI network analysis of coexpressed gene, and functional enrichment analysis. RESULTS: E2F1-8 expression increased in most cancers, including brain and CNS cancer. Higher expression in E2F1, 2, 4, 6, 7, and 8 indicated poor OS of LGG. Higher E2F3-6 and E2F1-8 expressions correlated with poor prognosis and increased immune infiltration levels in CD8+ T cells, macrophages, neutrophils, and DCs in GBM and CD8+ T cells, B cells, CD4+ T cells, neutrophils, macrophages, and DCs in LGG, respectively. CONCLUSION: E2F1-8 and E2F2-8 could be hopeful prognostic biomarkers of GBM and LGG, respectively. E2F3-6 and E2F1-8 could be likely therapeutic targets in patients with immune cell infiltration of GBM and LGG, respectively.

Diagnosing Balamuthia mandrillaris encephalitis via next-generation sequencing in a 13-year-old girl.

Balamuthia amoebic encephalitis has a subacute-to-chronic course and is almost invariably fatal owing to delayed diagnosis and a lack of effective therapy. Here, we report a 13-year-old girl with cutaneous lesions and multifocal granulomatous encephalitis. The patient underwent a series of tests and was suspected as having tuberculosis. She was treated with various empiric therapies without improvement. She was finally correctly diagnosed via next-generation sequencing of the cerebrospinal fluid. The patient deteriorated rapidly and died 2 months after being diagnosed with Balamuthia mandrillaris encephalitis. This study highlights the important clinical significance of next-generation sequencing, which provides better diagnostic testing for unexplained paediatric encephalitis, especially that caused by rare or emerging pathogens.

The correlation of PTPN4 expression with prognosis in breast cancer.

Precision medicine, applying knowledge of breast cancer's molecular subtypes, has improved the disease's prognosis. However, recurrence and chemoresistance are critical issues for breast cancer patients. PTPN4, a new potential therapeutic target, has not been studied sufficiently in breast cancer, and the potential role of PTPN4 in the prognosis of breast cancer patients is still unknown. In our study, data from 140 invasive breast cancer patients were retrospectively collected to identify the association between PTPN4 expression and clinical outcomes of these patients. The expressions of PTPN4 were detected by immunohistochemical analysis. Breast hyperplasia tissues showed higher expression of PTPN4. We found that PTPN4 expression was lower in breast cancer patients with relapse than in patients without relapse. Patients with an increased PTPN4 level had a significantly longer relapse-free survival and overall survival time. Decreased PTPN4 expression was an independent factor associated with relapse-free survival and overall survival, as shown by multivariate Cox regression analysis. The study found that PTPN4 is an attractive prognostic biomarker for predicting the clinical outcome and effective disease management of breast cancer patients.